7u9x
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Structure of PKA phosphorylated human RyR2-R2474S in the closed state== |
| - | <StructureSection load='7u9x' size='340' side='right'caption='[[7u9x]]' scene=''> | + | <StructureSection load='7u9x' size='340' side='right'caption='[[7u9x]], [[Resolution|resolution]] 2.58Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7u9x]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U9X FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u9x OCA], [https://pdbe.org/7u9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u9x RCSB], [https://www.ebi.ac.uk/pdbsum/7u9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u9x ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u9x OCA], [https://pdbe.org/7u9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u9x RCSB], [https://www.ebi.ac.uk/pdbsum/7u9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u9x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/RYR2_HUMAN RYR2_HUMAN]] Familial isolated arrhythmogenic ventricular dysplasia, right dominant form;Catecholaminergic polymorphic ventricular tachycardia;Familial isolated arrhythmogenic ventricular dysplasia, biventricular form;Familial isolated arrhythmogenic ventricular dysplasia, left dominant form. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/RYR2_HUMAN RYR2_HUMAN]] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.<ref>PMID:10830164</ref> <ref>PMID:20056922</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT results from stress-induced sarcoplasmic reticular Ca(2+) leak via the mutant RyR2 channels during diastole. We present atomic models of human wild-type (WT) RyR2 and the CPVT mutant RyR2-R2474S determined by cryo-electron microscopy with overall resolutions in the range of 2.6 to 3.6 A, and reaching local resolutions of 2.25 A, unprecedented for RyR2 channels. Under nonactivating conditions, the RyR2-R2474S channel is in a "primed" state between the closed and open states of WT RyR2, rendering it more sensitive to activation that results in stress-induced Ca(2+) leak. The Rycal drug ARM210 binds to RyR2-R2474S, reverting the primed state toward the closed state. Together, these studies provide a mechanism for CPVT and for the therapeutic actions of ARM210. | ||
| + | |||
| + | Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.,Miotto MC, Weninger G, Dridi H, Yuan Q, Liu Y, Wronska A, Melville Z, Sittenfeld L, Reiken S, Marks AR Sci Adv. 2022 Jul 22;8(29):eabo1272. doi: 10.1126/sciadv.abo1272. Epub 2022 Jul, 20. PMID:35857850<ref>PMID:35857850</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7u9x" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Marks AR]] |
| + | [[Category: Miotto MC]] | ||
Revision as of 03:19, 8 September 2022
Structure of PKA phosphorylated human RyR2-R2474S in the closed state
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